Open Access2,4-Dichlorobenzyl thiocyanate, an antimitotic agent that alters microtubule morphology.
Author(s) -
Irene Abraham,
Robert L. Dion,
Michael M. Gottesman,
Ernest Hamel
Publication year - 1986
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.83.18.6839
Subject(s) - tubulin , antimitotic agent , colcemid , microtubule , thiocyanate , chinese hamster ovary cell , chemistry , stereochemistry , biology , biochemistry , microbiology and biotechnology , receptor
A compound of simple structure, 2,4-dichlorobenzyl thiocyanate (DCBT), is an antimitotic agent with a number of unusual properties. The drug causes an extreme reorganization of microtubules in cells in culture. Most normal microtubules disappear, and remaining tubulin-containing structures appear to be bundled or aggregated. DCBT irreversibly inhibits in vitro polymerization of purified tubulin, but only after a prolonged preincubation of the protein with the drug. Binding of radiolabeled DCBT to tubulin similarly requires a long incubation time, with the reaction not being complete even after 6 hr at 37 degrees C. A specific interaction with tubulin is also shown by the crossresistance to DCBT of Colcemid-resistant cells with an altered beta-tubulin. A human KB carcinoma cell line and a Chinese hamster ovary cell line selected for crossresistance to multiple chemotherapeutic agents, including most antimitotic drugs, are sensitive to DCBT. Initial structure-function studies have demonstrated weak antimitotic and antitubulin activity with the parent compound benzyl thiocyanate. Chlorination at either position 2 or position 4 of the phenyl ring produces compounds of intermediate activity (4-chlorobenzyl thiocyanate is more active than 2-chlorobenzyl thiocyanate). The thiocyanate moiety appears to be essential for activity.